UCLA researchers have for the first time measured the activity of a brain region known to be involved in learning and memory during sleep and discovered that it behaves as if it’s remembering something, a finding that counters conventional theories about memory consolidation during sleep.
Mayank R. Mehta, senior author of a study that details the findings, said his team of researchers simultaneously measured the activity of single neurons from multiple parts of the brain involved in memory formation. This technique allowed them to determine which brain region was activating other areas of the brain and how that activation was spreading. Specifically, the researchers looked at three connected brain regions in mice – the new brain (the neocortex), the old brain (hippocampus), and the entorhinal cortex, an intermediate brain that connects the new and the old brains.
While previous studies have suggested that the dialogue between the old and the new brain during sleep was critical for memory formation, researchers had not investigated the contribution of the entorhinal cortex to this conversation.
Mehta’s team found that the entorhinal cortex showed what is called “persistent activity,” which is thought to mediate working memory during waking life – for example when people pay close attention to remember things temporarily, such as recalling a phone number or following directions. “The big surprise here is that this kind of persistent activity is happening during sleep, pretty much all the time,” Mehta said. “These results are entirely novel and surprising. In fact, this working memory-like persistent activity occurred in the entorhinal cortex even under anesthesia.”
“During sleep the three parts of the brain are talking to each other in a very complex way,” he explained. “The entorhinal neurons showed persistent activity, behaving as if they were remembering something even under anesthesia when the mice could not feel or smell or hear anything. Remarkably, this persistent activity sometimes lasted for more than a minute, a huge timescale in brain activity, which generally changes on a scale of one thousandth of a second.”
The findings, published in the journal Nature Neuroscience, challenge theories of brain communication during sleep, in which the hippocampus is expected to talk to, or drive, the neocortex. Mehta’s findings instead indicate that there is a third key actor in this complex dialogue, the entorhinal cortex, and that the neocortex is driving the entorhinal cortex, which in turn behaves as if it is remembering something. That, in turn, drives the hippocampus, while other activity patterns shut it down.
“This is a whole new way of thinking about memory consolidation theory. We found there is a new player involved in this process and it’s having an enormous impact,” Mehta said. “And what that third player is doing is being driven by the neocortex, not the hippocampus. This suggests that whatever is happening during sleep is not happening the way we thought it was. There are more players involved so the dialogue is far more complex, and the direction of the communication is the opposite of what was thought.”
Mehta theorizes that this process occurs during sleep as a way to unclutter memories and delete information that was processed during the day but is irrelevant. This results in the important memories becoming more salient and readily accessible. Notably, Alzheimer’s disease starts in the entorhinal cortex and patients have impaired sleep, so Mehta’s findings may have implications in that arena.
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